Folate Intake and the Risk of Neural Tube Defects: An Estimation of Dose-Response

Abstract

Folic acid supplements in the form of multivitamins, taken in the periconceptional period, lower the risk of neural tube defects (NTDs), but few studies have demonstrated a clear dose-response relationship. This prospective study analyzed data from 23,228 women, chiefly from the northeastern United States, who enrolled from 1984 through 1987. Diet and vitamin intake were assessed by telephone interviews early in the second trimester of pregnancy. Dietary folate was estimated using a 50-item food frequency questionnaire. Women using the highest-dose supplements in the first 5 weeks of pregnancy tended to be older and college-educated, and to have used multivitamins before becoming pregnant. They also were likelier than others to have a history of diabetes or a family history of NTDs. No dose-response relationship was noted when analyzing folic acid intake from supplements alone. The estimated reduction in NTD risk ranged froth 44% to 71%. Women with the lowest dietary folate intake had the highest risk of having an infant with an NTD (4 cases per 1000). There were indications that a higher intake of folate from foods is protective, but any protective effect was not linear. Women taking the least folate had a prevalence of NTDs of 3.4 cases per 1000. The risk declined as total folate increased, and the risk for those taking the most folate was 0.8 cases per 1000, a 77% reduction in risk. The prevalence of NTDs declined by 0.78 cases for every additional 500 dietary folate equivalents consumed per day. It appears that the NTD risk decreases substantially with a modest increase in total folate, from both food and supplements, in early pregnancy. Total folate intake is the critical parameter when formulating public health guidelines.